SF3B1

CHICAGO, Aug. 15, 2024 (GLOBE NEWSWIRE) -- Pathos AI, Inc. (www.pathos.com), a biotechnology company focused on revolutionizing precision medicine in cancer by harnessing the power of machine learning to transform drug development, announced today the world-wide license of PRT811, a potent, selective, and orally bioavailable brain penetrant SAM-competitive PRMT5 inhibitor from Prelude Therapeutics. PRT811 (renamed P-500) was developed by Prelude Therapeutics and completed a Phase 1 trial in March 2023. The trial enrolled patients with solid tumors including high-grade glioma and uveal melanoma and has potential application in other indications with high unmet need. Out of 16 patients with high-grade glioma with isocitrate dehydrogenase mutations (IDH+) in the Phase 1 trial, two confirmed complete responses (CR) were observed. At last follow-up, 1 response is ongoing and has lasted 31.0 months while the duration of response for the second CR patient was 7.5 months. Additionally, 1 patient achieved an unconfirmed partial response (PR). In addition, out of 23 uveal melanoma patients (10 patients with splicing factor 3B subunit 1 (SF3B1) splicing mutations and 13 without an SF3B1 mutation), one confirmed PR (duration of response of 10 months) and a second unconfirmed PR were observed, both in patients SF3B1 mutations. In the entire safety population (N=86), the most common adverse events of any grade, with an incidence of >20% were nausea (60.5%), vomiting (46.5%) fatigue (36.0%), constipation (29.1%), and thrombocytopenia (24.4%), and were predominantly grade 1-2. The most common adverse events (grade ≥3), occurring >5% were thrombocytopenia (9.3%), anemia (9.3%), and fatigue (5.8%). “These results from Prelude’s Phase 1 study are promising news for high-grade glioma patients and clinicians, who still have limited treatment options with chemotherapy and radiation that hasn’t changed in decades. With our AI Platform, we aim to increase the already encouraging response rate of P-500 through a novel biomarker-driven strategy, ultimately bringing this medicine to patients as efficiently as possible,” said Ryan Fukushima, Pathos CEO. “Prelude’s discovery engine has delivered a number of first- or best-in-class precision medicines including PRT811, a molecule that has shown early promise in the treatment of high-grade glioma. We are confident that Pathos AI, sharing our passion for precision medicine and commitment to serving cancer patients with high unmet need, is an ideal company to drive the development of this molecule forward for patients.” said Sean Brusky, Prelude CBO. "The resources from this transaction will support advancing Prelude's pipeline." About P-500P-500 (previously PRT811) is a selective, brain-penetrant small molecule inhibitor of protein arginine methyltransferase 5 (PRMT5) that has the potential to provide clinical benefit for patients with advanced solid tumors, including high-grade glioma and uveal melanoma. PRMT5 is an enzyme that adds methyl groups to proteins in cells using a molecule called S-adenosylmethionine (SAM) which regulates protein function and interactions. Several processes that support cancer cell growth and spread depend on PRMT5, making P-500 relevant not only to advanced high-grade glioma and uveal melanoma (in which objective responses to P-500 were observed in the Phase 1 clinical trial) but also to a number of other cancer indications. Preclinical studies have demonstrated PRMT5 inhibition can sensitize cancer cells to other treatments, expanding the application of P-500 to combination therapy in additional indications. About PathosPathos is a clinical-stage biotechnology company focused on re-engineering drug development, leveraging the power of AI technologies to bring precision medicines to market through partnership with biopharmaceutical companies. Pathos has raised $40 million to accelerate the development of precision medicines and to expand its platform, combining computational approaches across multimodal real-world data and patient-derived biological models. Additional information can be found at www.pathos.com. ContactsBusiness Development: bd@pathos.comPress Inquiries: press@pathos.com

Castle to present a second poster on its DecisionDx®-UM test sharing data from an ongoing prospective, multi-center study of patients with uveal melanoma (UM) led by the Collaborative Ocular Oncology Group (COOG2) FRIENDSWOOD, Texas--(BUSINESS WIRE)-- Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, today announced that it will present new data related to its DecisionDx-Melanoma and DecisionDx-UM tests at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, being held May 31-June 4, 2024, in Chicago. “Harnessing the biology of tumors through our DecisionDx family of gene expression pro can help guide decision-making about the most appropriate cancer treatment pathway for patients aligned to their risk of metastasis,” said Derek Maetzold, president and chief executive officer of Castle Biosciences. “The findings we are presenting at ASCO demonstrate the clinically meaningful risk stratification provided by our tests and support their utility in helping inform risk-aligned treatment and care for patients diagnosed with cutaneous and uveal melanoma to improve cancer outcomes.” Castle’s presentations at ASCO will take place during the Melanoma/Skin Cancers poster session on Saturday, June 1 from 1:30-4:30 p.m. Central time in Hall A. DecisionDx-Melanoma Title: The 31-GEP identifies patients with localized cutaneous melanoma at the highest risk of metastasis to the central nervous system Abstract: 9530 Poster Bd #: 314 Key take-aways: Cutaneous melanoma (CM) metastasis to the central nervous system (CNS) has a poor prognosis; however, patients generally experience better outcomes if CNS metastases are detected and treated earlier when the patient is still asymptomatic. CNS imaging is not routinely recommended for patients with early-stage CM (American Joint Committee on Cancer 8th edition (AJCC8) stage I–II), yet approximately 14% of patients with stage II melanoma will develop CNS metastases. This study demonstrated that the DecisionDx-Melanoma test can identify patients with earlier-stage melanoma who have a higher risk of CNS metastasis within the first three years post-diagnosis. These higher-risk patients may benefit from more frequent imaging surveillance to identify CNS metastases earlier to improve patient survival. Patients with Class 2B (highest risk) DecisionDx-Melanoma test results had higher rates of CNS metastases and lower five-year recurrence free survival than patients with Class 1A (lowest risk) or Class 1B/2A (increased risk) test results (p<0.001). Further, the study showed that a Class 2B (high risk) DecisionDx-Melanoma test result was the only significant predictor of CNS metastasis in multivariable analyses that included clinicopathologic-based risk factors considered in AJCC8 staging (HR (95% CI) 9.21 (2.72-31.19); p<0.001). DecisionDx-UM Title: The 15-gene expression pro is independent from PRAME and 7-gene next-generation sequencing: Results from 3,267 clinically tested uveal melanomas Abstract: 9598 Poster Bd #: 382 Key take-aways: This study is the largest to date to describe the combined performance of Castle’s comprehensive suite of UM tests, which includes the prognostic DecisionDx-UM test and two ancillary tests: Preferentially Expressed Antigen in Melanoma (PRAME) status (DecisionDx-PRAME) and DNA mutation status (DecisionDx-UMSeq). The study explored associations across test results and found that neither PRAME expression status nor the presence of mutations in putative prognostic genes (BAP1, SF3B1 and EIF1AX) to be adequate surrogates for the DecisionDx-UM Class result. Given the extensive data supporting DecisionDx-UM as the most accurate predictor of metastatic outcomes, including recently presented data from the largest prospective performance study of DecisionDx-UM to date, which included more than 1,500 patients from 26 centers, study authors recommend that PRAME and DNA mutation status be considered in the context of a DecisionDx-UM result to further refine metastatic risk and inform risk-aligned treatment plans. The full abstracts outlined above can be found at the ASCO website here. About DecisionDx-Melanoma DecisionDx-Melanoma is a gene expression pro stratification test. It is designed to inform two clinical questions in the management of cutaneous melanoma: a patient’s individual risk of sentinel lymph node (SLN) positivity and a patient's personal risk of melanoma recurrence and/or metastasis. By integrating tumor biology with clinical and pathologic factors using a validated proprietary algorithm, DecisionDx-Melanoma is designed to provide a comprehensive and clinically actionable result to guide risk-aligned patient care. DecisionDx-Melanoma has been shown to be associated with improved patient survival and has been studied in more than 10,000 patient samples. DecisionDx-Melanoma’s clinical value is supported by 50 peer-reviewed and published studies, providing confidence in disease management plans that incorporate the test’s results. Through March 31, 2024, DecisionDx-Melanoma has been ordered more than 164,000 times for patients diagnosed with cutaneous melanoma. More information about the test and disease can be found here. About DecisionDx-UM DecisionDx-UM is Castle Biosciences’ 15-gene expression profile (GEP) test that uses an individual patient’s tumor biology to predict individual risk of metastasis in patients with uveal melanoma (UM). DecisionDx-UM is the standard of care in the management of newly diagnosed UM in the majority of ocular oncology practices in the United States. Since 2009, the American Joint Committee on Cancer (AJCC; v7 and v8) Staging Manual for UM has specifically identified the GEP test as a prognostic factor that is recommended for collection as a part of clinical care. Further, the National Comprehensive Cancer Network (NCCN) guidelines for UM include the DecisionDx-UM test result as a prognostic method for determining risk of metastasis and recommend differential surveillance regimens based on a Class 1A, 1B and 2 result. DecisionDx-UM is currently the only prognostic test for UM that has been validated in prospective, multi-center studies, and it has been shown to be a superior predictor of metastasis compared to other prognostic factors, such as chromosome 3 status, mutational status, AJCC stage and cell type. It is estimated that nearly 8 in 10 patients diagnosed with UM in the United States receive the DecisionDx-UM test as part of their diagnostic workup. More information about the test and disease can be found here. About Castle Biosciences Castle Biosciences (Nasdaq: CSTL) is a leading diagnostics company improving health through innovative tests that guide patient care. The Company aims to transform disease management by keeping people first: patients, clinicians, employees and investors. Castle’s current portfolio consists of tests for skin cancers, Barrett’s esophagus, mental health conditions and uveal melanoma. Additionally, the Company has active research and development programs for tests in other diseases with high clinical need, including its test in development to help guide systemic therapy selection for patients with moderate-to-severe atopic dermatitis, psoriasis and related conditions. To learn more, please visit and connect with us on LinkedIn, Facebook, X and Instagram. DecisionDx-Melanoma, DecisionDx-CMSeq, DecisionDx-SCC, MyPath Melanoma, DiffDx-Melanoma, TissueCypher, IDgenetix, DecisionDx-UM, DecisionDx-PRAME and DecisionDx-UMSeq are trademarks of Castle Biosciences, Inc. Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, which are subject to the “safe harbor” created by those sections. These forward-looking statements include, but are not limited to, statements concerning: (i) the ability of the DecisionDx-Melanoma test to identify patients with earlier-stage melanoma who have a higher risk of CNS metastasis within the first three years post-diagnosis and (ii) the ability of DecisionDx-UM test to accurately predict metastatic outcomes. The words “believe,” “can,” “could,” “potential” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements that we make. These forward-looking statements involve risks and uncertainties that could cause our actual results to differ materially from those in the forward-looking statements, including, without limitation: subsequent study or trial results and findings may contradict earlier study or trial results and findings or may not support the results obtained in these studies, including with respect to the discussion of our tests in this press release; actual application of our tests may not provide the aforementioned benefits to patients; and the risks set forth under the heading “Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2023, our Quarterly Report on Form 10-Q for the quarter ended March 31, 2024 and in our other filings with the SEC. The forward-looking statements are applicable only as of the date on which they are made, and we do not assume any obligation to update any forward-looking statements, except as may be required by law.

Pictured: Doctor aspirating a patient's bone marrow/iStock, Vadym Terelyuk Roivant Sciences announced Tuesday during its third-quarter financial report that it will discontinue the development of its investigational SF3B1 modulator RVT-2001, following an interim analysis of a Phase I/II study in myelodysplastic syndromes. “Unfortunately, the data generated in the Phase I/II study did not meet our bar for progressing,” Roivant CEO Matt Gline said during Tuesday’s investor call. “And so, we’ve decided to discontinue development of RVT-2001 after an interim analysis of that data.” Roivant had invested a “reasonable modest low double-digit million-dollar sum” on RVT-2001, Gline added. “I think just sometimes these things don’t work out the way you want scientifically, and so, we’re trying to be efficient in making those decisions.” Roivant first formed Hemavant two years ago to the day. Launched in February 2022, Hemavant’s main goal was to advance RVT-2001 as a potential first-in-class treatment for transfusion-dependent anemia in patients with lower-risk myelodysplastic syndromes (MDS). MDS are a group of cancers in which immature blood cells in the bone marrow do not mature or become healthy blood cells. Medications or bone marrow transplants may lessen transfusion needs and slow or prevent progression to leukemia. RVT-2001, which Roivant licensed from Eisai in January 2022, was a potentially first-in-class orally available small molecule modulator of the splicing factor 3B subunit 1 (SF3B1). Eisai had conducted an 84-participant Phase I study of RVT-2001—which was previously dubbed H3B-8800—and found “no complete or partial responses.” Tuesday’s decision to discontinue RVT-2001 breaks a winning streak for Roivant. In July 2023, The Wall Street Journal reported that Roche was looking to snap up Roivant’s late-stage anti-TL1A antibody RVT-3101, which had aced it Phase IIb study just a month earlier. At 56 weeks, 36% of ulcerative colitis patients treated with RVT-3101 achieved clinical remission. Roche confirmed the reports in October 2023. For $7.1 billion upfront and the promise of $150 million in near-term milestones, the pharma acquired Roivant subsidiary Televant Holdings, which was principally responsible for advancing RVT-3101 in inflammatory bowel diseases. Aside from RVT-3101, Roivant’s Immunovant also secured a Phase I victory in September 2023. In the early-stage study, its investigational autoimmune antibody IMVT-1402 led to dose-dependent reductions in IgG levels; IMVT-1402 either matched or outperformed Immunovant’s other experimental asset batoclimb. IMVT-1402 elicits the degradation of IgG auto-antibodies by binding to FcRn, which makes it a potential treatment for the more than two million people with conditions driven by IgG auto-antibodies, Immunovant said at the time. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.